Intra-aortic renal drug delivery catheter

ABSTRACT

A catheter for delivering a therapeutic or diagnostic agent to a branch blood vessel of a major blood vessel, generally comprising an elongated shaft having at least one lumen in fluid communication with an agent delivery port in a distal section of the shaft, an expandable tubular member on the distal section of the shaft, and a radially expandable member on the tubular member. The tubular member is configured to extend within the blood vessel up-stream and down-stream of a branch vessel, and has an interior passageway which is radially expandable within the blood vessel to separate blood flow through the blood vessel into an outer blood flow stream exterior to the tubular member and an inner blood flow stream within the interior passageway of the tubular member.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of copending U.S. patent applicationSer. No. 09/724,691 filed on Nov. 28, 2000, incorporated by referenceherein.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable

INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A COMPACT DISC

Not Applicable

BACKGROUND OF THE INVENTION

This invention relates to the field of medical devices, and moreparticularly to a catheter configured for drug delivery.

Acute renal failure (“ARF”) is an abrupt decrease in the kidney'sability to excrete waste from a patient's blood. This change in kidneyfunction may be attributable to many causes. A traumatic event, such ashemorrhage, gastrointestinal fluid loss, or renal fluid loss withoutproper fluid replacement may cause the patient to go into ARF. Patientsmay also become vulnerable to ARF after receiving anesthesia, surgery,or α-adrenergic agonists because of related systemic or renalvasoconstriction. Additionally, systemic vasodilation caused byanaphylaxis, and antihypertensive drugs, sepsis or drug overdose mayalso cause ARF because the body's natural defense is to shut down, i.e.,vasoconstrict, non-essential organs such as the kidneys. Reduced cardiacoutput caused by cardiogenic shock, congestive heart failure,pericardial tamponade or massive pulmonary embolism creates an excess offluid in the body, which can exacerbate congestive heart failure. Forexample, a reduction in blood flow and blood pressure in the kidneys dueto reduced cardiac output can in turn result in the retention of excessfluid in the patient's body, leading, for example, to pulmonary andsystemic edema.

Previously known methods of treating ARF, or of treating acute renalinsufficiency associated with congestive heart failure (“CHF”), involveadministering drugs. However, many of these drugs, when administered insystemic doses, have undesirable side effects. Additionally, many ofthese drugs would not be helpful in treating other causes of ARF. Whilea septic shock patient with profound systemic vasodilation often hasconcomitant severe renal vasoconstriction, administering vasodilators todilate the renal artery to a patient suffering from systemicvasodilation would compound the vasodilation system wide. In addition,for patients with severe CHF (e.g., those awaiting heart transplant),mechanical methods, such as hemodialysis or left ventricular assistdevices, may be implemented. Mechanical treatments, such ashemodialysis, however, generally have not been used for long-termmanagement of CHF. Such mechanical treatments would also not be help forpatients with strong hearts suffering from ARF.

Intra-aortic balloon pumps (IABPs) have been suggested for use indiverting blood flow into branch arteries. One such technique involvesplacing an IABP in the abdominal aorta so that the balloon is situatedslightly below (proximal to) the branch arteries. The balloon isselectively inflated and deflated in a counterpulsation mode so thatincreased pressure distal to the balloon directs a greater portion ofblood flow into the branch arteries. Although the IABP method ofcounterpulsation may be effective for increasing coronary perfusion, itwould not extend well to the renal arteries.

It would be a significant advance to provide an intra-aortic catheterfor improved delivery of agents to a branch vessel such as a renalartery.

SUMMARY OF THE INVENTION

The invention is directed to a catheter controlling the flow of blood ina major blood vessel to a branch blood vessel, and particularly fordelivering a therapeutic or diagnostic agent to the branch blood vesselwith the blood flow thereto. The catheter generally comprises anelongated shaft, an expandable tubular member on a distal section of theshaft, and a radially expandable member on the expandable tubularmember. Preferably, the elongated shaft has at least one lumen in fluidcommunication with an agent delivery port in a distal section of theshaft. The expandable tubular member is configured to extend within amajor blood vessel up-stream and down-stream of a branch vessel, and hasan interior passageway which is radially expandable within the majorblood vessel to separate blood flow through the major blood vessel intoan outer blood flow stream exterior to the tubular member and an innerblood flow stream within the interior passageway of the tubular member.Thus, the expandable tubular member provides a perfusion passageway inthe major blood vessel. The radially expandable member is locateddown-stream of the agent delivery port and is positioned down-stream ofthe branch artery, and has an expanded configuration with an outerdiameter larger than an outer diameter of the expanded tubular memberlocated up-stream thereto. In the expanded configuration, the radiallyexpandable member is configured constrict blood flow past an outersurface of the radially expandable member and direct at least part ofthe blood flow in the outer blood flow stream into the branch vessel,which, consequently, decreases the blood flow in the outer blood flowstream down-stream of the branch vessel. The catheter of the inventionprovides for delivery of an agent to a side branch vessel of a majorvessel, and continuous perfusion of the major blood vessel. Anotheraspect of the invention is directed to methods of delivering atherapeutic or diagnostic agent to one or both kidney's of a patient.

The term proximal should be understood to mean locations on the catheterrelatively closer to the operator during use of the catheter, and theterm distal should be understood to mean locations on the catheterrelatively further away from the operator during use of the catheter.The term up-stream should be understood to mean locations on thecatheter relatively further upstream in the blood flow within the bloodvessel, when the catheter is in place in the patient's blood vessel. Theterm down-stream should be understood to mean locations on the catheterrelatively further down-stream in the blood flow within the bloodvessel, when the catheter is in place in the patient's blood vessel.

The tubular member interior passageway defines a perfusion or bloodpass-through lumen. The interior passageway is radially expandable, sothat the tubular member can be expanded from an unexpanded configurationproviding a low profile for insertion and advancement of the catheterwithin the patient's blood vessel, to an expanded configurationproviding a desired level of perfusion within the blood vessel. Theexpanded interior passageway of the tubular member is sufficiently largeto avoid or limit detrimental effects of occluding the blood vessel, andspecifically, in one embodiment, the effects of infrarenal aorticocclusion. However, in addition to the inner blood flow stream withinthe inner lumen of the tubular member, the tubular member has an outerdiameter in the expanded configuration along at least a section thereofwhich is configured to allow for an outer blood flow stream exterior tothe tubular member which is at least in part directed or flowing to thebranch vessel. As a result, the catheter can be used to deliver an agentfrom the agent delivery port into the outer blood flow stream and to thepatient's branch vessel.

The tubular member can be expanded by a variety of suitable methods. Inone embodiment, the tubular member is self-expanding. For example, aradially collapsed tubular member is expanded by release of a radiallycompressive force, as for example, by removal of a sheath of guidecatheter from around the tubular member. Similarly, a wound or foldedtubular member is expanded by allowing the member to unwind or unfoldinto the expanded tubular configuration. In a presently preferredembodiment, the tubular member comprises a cylindrical inflatable memberformed of a plurality of fluid-communicating wall chambers, which isinflated by directing inflation fluid into the wall chambers. In anotherembodiment, the tubular member has a braided structure, which isexpanded by retracting a pull line to thereby shorten the length of thebraided structure. In another embodiment, the tubular member is aballoon, which is expanded by directing inflation fluid into an wallchamber of the tubular member.

The radially expandable member is on a proximal or down-stream sectionof the tubular member, and is configured to restrict blood flow in theblood vessel. The radially expandable member has an expandedconfiguration with a larger outer diameter than the expanded tubularmember. The radially expandable member may be a separate member securedto the tubular member as for example, where the radially expandablemember is a balloon secured to an outer surface of a tubular member.Alternatively, the radially expandable member may be an integral part ofthe tubular member so that the tubular member and radially expandablemember are a one-piece unit of the catheter, as for example, where thetubular member is a frame or braided structure having a sheath thereonand the radially expandable member is a radially enlarged section of thetubular member which expands as the tubular member expands, or where thetubular member is cone shaped and the radially expandable member is thelargest diameter section of the cone shaped tubular member.

In the expanded configuration, the radially enlarged member isconfigured to decrease blood flow in the outer blood flow streamdown-stream of the branch vessel. Thus, a relatively large concentrationof agent is delivered into the branch vessel from the agent deliveryport, in comparison to the amount of agent allowed to flow through theblood vessel down-stream of the branch vessel. In one embodiment, theradially expandable member has an expanded outer diameter configured topartially occlude, i.e., restrict but not completely block, the outerblood flow stream in the blood vessel. Thus, a portion of the outerblood flow through the blood vessel is allowed to flow around anddown-stream of an outer surface of the radially expandable member.However, in an alternative embodiment, the radially expandable memberhas an outer diameter configured to contact a wall of the blood vesseland thereby occlude the outer blood flow stream in the blood vesseldown-stream of the branch vessel.

Thus, the catheter of the invention separates the blood flow through theblood vessel into an outer blood flow stream directed in part into thebranch vessel having a relatively high concentration of agent, and aninner blood flow stream. The end of the tubular member positionedup-stream of the branch vessel is located up-stream of agent deliveryport in the shaft, so that the inner blood flow stream within thetubular member has a relatively low amount of or no agent. Moreover,with the radially expandable member in the expanded configuration, theblood flow exterior to the tubular member down-stream of the branchvessel is decreased in comparison to the blood flow stream exterior tothe tubular member up-stream of the branch vessel. As a result, theamount of agent in the outer blood flow stream directed into the branchvessel is improved.

The catheter of the invention can be used to deliver a variety oftherapeutic or diagnostic agents to the patient's blood vessel. In oneembodiment, vasoactive and/or renal protective agents such asPapaverine, are delivered to the renal arteries for treatment of ARF andfluid overload. Other preferred agents include Calcium-channel blockerssuch as nifedipine or verapamil, and fenoldapam, a dopamine DA₁ agonist.The tubular member inner lumen providing a perfusion pathway allows thecatheter to be in place in the patient's blood vessel for extendedperiods of treatment. The period of treatment will depend on theapplication and the agent, but is typically about 2 to about 72 hours,preferably about 4 to about 8 hours.

The catheter of the invention provides improved agent delivery to abranch vessel with continuous perfusion of the major blood vessel due tothe relatively large perfusion lumen in the tubular member. Thus,possible detrimental effects of infrarenal aortic occlusion are reducedor prevented. Moreover, the catheter of the invention provides arelatively large concentration of agent to the renal arteries withlittle loss of blood flow through the aorta to the lower limbs. Thecatheter configured for intra-aortic delivery of an agent provides forrelatively quick, intraluminal placement of the catheter. These andother advantages of the invention will become more apparent from thefollowing detailed description of the invention and the accompanyingexemplary drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an elevational view, partially in section, of a catheter whichembodies features of the invention, illustrating the expandable tubularmember and balloon in an unexpanded configuration.

FIG. 2 is an enlarged view, partially in phantom, of a distal section ofthe catheter shown in FIG. 1, with the tubular member in the expandedconfiguration.

FIG. 3 is an enlarged view, partially in phantom, of a distal section ofthe catheter shown in FIG. 2, illustrating the catheter in the patient'sdescending aorta proximate the renal arteries, with the balloon in theinflated configuration.

FIG. 4 is a transverse cross sectional view of the balloon shown in FIG.3, taken along line 4-4.

FIG. 5 is a transverse cross sectional view of the balloon shown in FIG.3, taken along line 5-5.

FIG. 6 is a transverse cross sectional view of the balloon shown in FIG.3, taken along line 6-6.

FIG. 7 is an enlarged view, partially in phantom, of a distal section ofan alternative embodiment having an expandable tubular member comprisinga sheath covered collapsible frame.

FIG. 8A is a transverse cross sectional view of an alternativeembodiment having an expandable tubular member with a small profilewrapped configuration.

FIG. 8B is a transverse cross sectional view of the tubular member shownin FIG. 8A, illustrating the tubular member in the expanded unwrappedconfiguration.

FIG. 9A is a transverse cross sectional view of an alternativeembodiment having an expandable tubular member with a small profilewound configuration

FIG. 9B is a transverse cross sectional view of the tubular member shownin FIG. 9A, illustrating the tubular member in the expanded unwoundconfiguration.

FIG. 10 illustrates an enlarged view of a distal section of analternative embodiment having an expandable tubular member comprising aplurality of inflatable wall chambers or balloons secured together toform the tubular member.

FIG. 11 is a transverse cross sectional view of the catheter shown inFIG. 10, taken along line 11-11.

FIG. 12 is a transverse cross sectional view of the catheter shown inFIG. 10, taken along line 12-12.

FIG. 13 illustrates an enlarged view of a distal section of analternative embodiment having an expandable tubular member comprising aplurality of fluid-communicating wall chambers, wherein the tubularmember has a conical shape.

FIG. 14 is an elevational view of fused polymeric sheets used to formthe tubular member, having curved seal lines forming thefluid-communicating chambers.

FIG. 15 is a transverse cross-sectional view of a tubular member formedof the sheets illustrated in FIG. 14.

FIG. 16 is a transverse cross-sectional view of an alternativeembodiment of an expandable tubular member comprising a plurality ofinflatable balloons within an outer sheath.

FIG. 17 is an enlarged view, partially in phantom, of a distal sectionof an alternative embodiment having a radially expandable membercomprising a radially enlarged section of the expandable tubular member.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 illustrates a catheter 10 which embodies features of theinvention, generally comprising an elongated shaft 11 having a proximalend, a distal end, and at least one lumen 12 extending therein, atubular member 13 on a distal section of the catheter shaft 11 and aradially expandable member 14 on the tubular member 13. Adapter 15 onthe proximal end of the shaft provides access to the catheter lumen.FIG. 1 illustrates the tubular member and the radially expandable memberin low profile, unexpanded configurations for entry into the patient'sblood vessel.

In the embodiment illustrated in FIG. 1, the radially expandable member14 comprises an inflatable balloon. The balloon has proximal and distalends secured to an outer surface of the tubular member 13, and aninterior in fluid communication with an inflation lumen 21 (FIG. 4) inthe shaft 11. The balloon 14 can be formed of a variety of suitablematerials typically used in the construction of catheter occlusionballoons, and in a presently preferred embodiment is highly compliantand is formed of a material such as latex, polyisoprene, polyurethane, athermoplastic elastomer such as C-Flex. In alternative embodiment, theballoon may be noncompliant or semi-compliant. While discussed belowprimarily in terms of a radially expandable member comprising a balloon,it should be understood that the radially expandable member may have avariety of suitable configurations.

In the embodiment illustrated in FIG. 1, the tubular member 13 comprisesbraided filaments 16, such as wire, ribbon, and the like, having asheath 17, and having a lumen or interior passageway 18 therein. A pullline 19 having a distal portion secured to the tubular member isconfigured to be retracted or pulled proximally to radially expand thetubular member 13. Specifically, the braided filaments 16 can reorientfrom a longer, smaller diameter configuration and a shorter, largerdiameter configuration cause the tubular member to shorten, therebyradially expanding the tubular member 13. When the pull line is notunder tension, the spring force of the elastomeric material of thesheath 17 will cause the tubular body defined by the braided filaments16 to elongate and reduce in diameter. The sheath 17 is preferably anelastomeric polymer on the braided filaments. The sheath 17 can be on aninner or outer surface of the braided filaments, or the braidedfilaments can be completely or partially embedded within the sheath 17.In the embodiment in which the sheath is on a surface of the filaments,the sheath is preferably secured to a surface of the filaments as forexample with adhesive or heat bonding. The braided filaments 16 can beformed of a variety of suitable materials such as metals or stiffpolymers. A variety of suitable polymeric materials can be used to formthe sheath 17. While discussed below primarily in terms of a tubularmember comprising a braided tube, it should be understood that thetubular member may have a variety of suitable configurations.

FIG. 2 illustrates the tubular member 13 in the expanded configurationafter retraction of the pull line 19. As best illustrated in FIG. 2,showing the distal section of the shaft 11 within the inner lumen of thetubular member 13 in dotted phantom lines, the distal end of the shaft11 is located proximal to the distal end of the expanded tubular member13. In the embodiment illustrated in FIG. 2, the balloon 14 is in anonexpanded configuration. The section of the tubular member under theballoon is illustrated in dashed phantom lines.

FIG. 3 illustrates the catheter 10 with the balloon 14 in the expandedconfiguration. As best illustrated in FIGS. 4-6 showing transverse crosssections of the catheter shown in FIG. 3, taken along lines 4-4, 5-5,and 6-6, respectively, the shaft has an inflation lumen 21 extendingfrom the proximal end of the shaft 11 to an inflation port 22 (FIG. 5)located on the shaft distal section, in fluid communication with theinterior of the balloon. Arm 23 on adapter 15 provides access to theinflation lumen 21, and is in fluid communication with a source ofinflation fluid (not shown). The shaft also has an agent delivery lumen24 extending from the proximal end to an agent delivery port 25 in thedistal end of the shaft 11. Arm 26 on adapter 15 provides access to theagent delivery lumen 24, and is in fluid communication with an agentsource (not shown). The tubular member sheath 17 has an agent deliveryopening 26 adjacent to the shaft agent delivery port 25, for providing apathway for agent delivery from the lumen 24 to exterior to the tubularmember 13. In the illustrated embodiment, the inflation lumen 21 andagent delivery lumen 24 are side-by-side in a multilumen shaft 11, withinflation port 22 extending through a side wall of the shaft. However, avariety of suitable configurations may be used as are conventionallyused in catheter shaft design including coaxial lumens in fluidcommunication with side ports or ports in the distal extremity of theshaft. The agent delivery port 25 is preferably in a side wall of theshaft 11 distal section in fluid communication with the agent deliverylumen 24, however, alternatively, the agent delivery port 25 may be inthe distal end of the shaft 11.

FIG. 3 illustrates the catheter 10 in a blood vessel 31, such as adescending aorta, of a patient, having branch vessels 32, such as therenal arteries, opening therein. The catheter 10 is introduced andadvanced within the patient's blood vessel 31 in the low profile,unexpanded configuration illustrated in FIG. 1. The agent delivery port25 is positioned proximate to (up-stream or in line with) the one ormore branch vessels 32, and the distal end of the tubular member ispreferably up-stream of the one or more branch vessels 32. The tubularmember is then expanded to the expanded configuration, and, preferably,thereafter the balloon 14 is radially expanded by directing inflationfluid into the balloon interior. Specifically, in one embodiment of amethod of the invention for delivery of a therapeutic or diagnosticagent to one or more of a patient's kidneys, the catheter is introducedinto the femoral artery, as for example by the Seldinger technique,preferably slidingly over a guidewire (not shown), and advanced into thedescending aorta 31. Although not illustrated, the shaft may be providedwith a separate guidewire lumen, or the catheter may be advanced over aguidewire in agent delivery lumen 24 adapted to slidingly receive aguidewire. Alternatively, the catheter 10 may be advanced without theuse of a guidewire. The agent delivery port 25 is positioned proximateto one or both renal arteries 32, as illustrated in FIG. 3, and thetubular member 13 extends within the aorta 31 up-stream and down-streamof the renal arteries 32. The tubular member 13 is radially expanded byretracting pull line 19. The interior passageway 18 of the tubularmember 13 separates blood flow through the blood vessel 31 into an outerblood flow stream 33 exterior to the tubular member 13, and in innerblood flow stream 34 within the interior passageway 18 of the tubularmember 13. The balloon 14 is expanded by directing inflation fluid intothe inflation lumen. In the embodiment illustrated in FIG. 3, theballoon 14 is expanded to an outer diameter which does not completelyocclude the patient's aorta 31. However, in an alternative embodiment,the balloon expands into contact with the wall of the aorta 21, to anouter diameter which completely occludes the aorta 31 (not shown).Balloon 14 may have a length and elongated configuration configured toprovide mechanical stability for and coaxial centering of the operativedistal section of the catheter in the blood vessel 31. A stabilizingmember (not shown) may be provided on an outer surface of the distal endof the tubular member 13, such as for example unfoldable arms whichanchor the distal end of the catheter in the aorta 31 during delivery ofagent. A variety of suitable imaging modalities may be used to positionthe catheter in the desired location in the blood vessel, such asfluoroscopy, or ultrasound. For example, radiopaque markers (not shown)on the shaft may be used in positioning the radially expandable member14 and agent delivery port 25 at the desired location in the bloodvessel 31.

A therapeutic or diagnostic agent (hereafter “agent”) is delivered tothe renal arteries 32 by introducing the agent into the agent deliverylumen 24 in the shaft 11, and out the agent delivery port 25. An agentdelivery opening 26 in the tubular member 13 adjacent to the agentdelivery port 25 provides a pathway for agent delivery from lumen 24 toexternal to the tubular member 13. The agent delivery port 25 isup-steam of the renal arteries 32 and proximal to the distal end of thetubular member 13. Thus, the outer blood flow stream 33 has a relativelyhigh concentration of agent and the inner blood flow stream 34 has arelatively low concentration or no agent. Additionally, the balloon 14in the expanded configuration restricts the flow of blood to decreasethe blood flow exterior to the proximal portion of the tubular member 13down-stream of the renal arteries 32 in comparison to the blood flowstream exterior to the distal portion of the tubular member 13 up-streamof the renal arteries 32. As a result, a relatively large amount of theagent delivered from the agent delivery port 25 is directed into therenal arteries 32, in comparison to the amount of agent which flowsdown-stream of the renal arteries 32 in the aorta 31.

In one embodiment, the outer blood flow stream is substantial.Preferably, the cross-sectional area of the inner lumen 18 of thetubular member 13 is about 4% to about 64% of the blood vessel 31 (i.e.,aorta) cross-sectional area, or about 4 mm to about 16 mm for a bloodvessel 31 having a 20 mm inner diameter. It should be noted that in someembodiments, the cross-sectional area of the wall of the tubular member13 is not insignificant in relation to the cross-sectional area of theblood vessel 31. In the embodiment illustrated in FIG. 1 in whichtubular member 13 comprises sheath 17 on a frame of filaments 16, thiscross-sectional area is negligible. In alternative embodiments discussedbelow, such as the embodiments illustrated in FIGS. 10 and 13, thecross-sectional area of the wall of the tubular member 13 may be about2% to about 50%, more specifically about 5% to about 20%, of thecross-sectional area of a section of the blood vessel 31 located at theup-stream most end of the catheter 10. Additionally, the aorta hasmultiple branch vessels in addition to the renal arteries which effectthe total flow in the aorta at a given location therein. Thus, apercentage of the blood flow that enters the abdominal aorta, i.e., pastthe diaphragm, is delivered in the normal rest state of circulation tothe celiac trunk, the superior and inferior mesenteric arteries, and therenal arteries. Nonetheless, the flow segmentation created by thepresence of the deployed catheter 10 is such that the blood flow in theouter blood flow stream of a patient at rest is about 10% to about 90%of the total blood flow immediately up-stream of the up-stream or distalmost end of the tubular member 13, i.e., of the total blood flow presentin the section of the aorta immediately adjacent to the renal arteries.Similarly, the blood flow in the inner blood flow stream of a patient atrest is about 10% to about 90% of the total blood flow immediatelyup-stream of the up-stream or distal most end of the tubular member 13.The flow in the outer blood flow stream is sufficient to provideadequate kidney function, although the flow required will vary dependingupon factors such as the presence of drugs which increase flow orincrease the ability of the tissue to withstand ischemic conditions.

While the renal arteries are illustrated directly across from oneanotherin FIG. 3, and the method is discussed primarily in terms of delivery ofagent to both renal arteries together, it should be understood that thecatheter may be positioned and used to deliver agent to the renalarteries individually, and specifically in anatomies having the renalarteries longitudinally displaced from oneanother. The flow of agent isthen stopped. The tubular member 13 is contracted by urging the pullline distally, and the balloon 14 is collapsed by removal of theinflation fluid, and the catheter removed from the patient.

A variety of suitable radially expandable tubular members 13 may be usedin the catheter 10 of the invention. FIG. 7 illustrates an alternativeembodiment of distal end of the catheter 10 in which the tubular member13 comprises a self-expanding frame 40 having a sheath 41 thereon. Asdiscussed above in relation to the embodiment of FIG. 1, catheter shaft11 defines an inflation lumen and an agent delivery lumen, and radiallyexpandable member comprises a balloon 42 on an outer surface of sheath41. For ease of illustration, the balloon 42 is shown as a transparentmaterial. In the embodiment illustrated in FIG. 7, catheter shaft 11comprises a multilumen proximal shaft 43 defining proximal sections ofthe inflation lumen 21 and agent delivery lumen 24, a first distaltubular member 44 defining a distal section of inflation lumen 21extending to inflation port 22, and a second distal tubular member 46defining a distal section of agent delivery lumen 24 extending to agentdelivery port 25. First tubular member 44 extends distally from thedistal end of the proximal section of the inflation lumen in themultilumen proximal shaft. Similarly, second tubular member 46 extendsdistally from the distal end of the proximal section of the agentdelivery lumen in the multilumen proximal shaft. First and secondtubular members 44/46 are typically formed of thin-walled polymericmaterial such as polyimide, with an inner diameter of about 0.002 inchto about 0.006 inch, and a wall thickness of about 0.0005 inch and about0.002 inch. In alternative embodiments, catheter shaft comprises anouter tubular member with first and second inner tubular membersdefining inflation lumen and agent delivery lumen, respectively,extending within the outer member and out the distal end thereof. Theagent delivery lumen 24 extends to a location proximal to the distal endof the tubular member 13 and distal to the balloon. One or more agentdelivery ports 25 are provided in a distal section of the agent deliverylumens, as discussed above in relation to the embodiment of FIG. 1. Inalternative embodiments, one or more additional agent delivery lumensmay be provided.

In the illustrated embodiment, the frame 40 comprises longitudinallyextending filaments or struts, such as wires, joined together at theproximal and distal ends thereof. In a preferred embodiment, frame 40 isformed of high strength metal, such as stainless steel, nickel-titaniumalloy, and titanium. However a variety of suitable materials can be usedincluding rigid polymers. The filaments typically have a roundtransverse cross section, with a diameter of about 0.006 inch to about0.016 inch, or a rectangular transverse cross section with a thicknessof about 0.001 inch to about 0.006 inch and a width of about 0.006 inchto about 0.016 inch. Sheath 41 is similar to sheath 17 discussed inrelation to the embodiment of FIG. 1, and is preferably a thin walledelastomeric tubular member. The tubular member 13 is illustrated in FIG.7 in the expanded configuration. The frame 40 is radially collapsible toa low profile configuration with the sheath 41 in a folded or pleatedcompact configuration for advancement within the patient's blood vessel.Once in place at a desired location within the blood vessel, arestraining member which applies a radially compressive force, whichholds the frame in the collapsed smaller diameter configuration, isremoved so that the frame expands. The frame may be held in thecollapsed smaller diameter configuration by a variety of suitablerestraining members such as a delivery catheter or removable outersheath. For example, in one embodiment, the frame is deformed into thesmaller diameter configuration within the lumen of a delivery catheter49, and then expanded in the blood vessel lumen by longitudinallydisplacing the frame out the distal end of the delivery catheter 49 tothereby remove the radially compressive force of the delivery catheter49. Although not illustrated, a pull line similar to pull line 19discussed above in relation to the embodiment of FIG. 1 may be providedto apply additional radially expanding force to the filaments tosupplement their inherent spring force, and is preferably provided inthe embodiments having a radially expandable member 14 comprising aninflatable balloon where inflation of the balloon creates a radiallycompressive force on the tubular member 13.

In the embodiment illustrated in FIG. 7, balloon 42 is inflated intocontact with the aorta wall 31 to an outer diameter which completelyoccludes the outer blood flow stream downstream of the renal arteries32. Thus, the outer blood flow stream is directed into the branchvessels 32. However, the balloon may be configured to inflate to anouter diameter which does not completely occlude the downstream outerblood flow stream, as discussed above in relation to the embodiment ofFIG. 3.

FIGS. 8 and 9 illustrate transverse cross sectional views of analternative embodiment in which the tubular member 13 comprises a sheet50 configured to unwind from a wound low profile to an unwound radiallyexpanded configuration to thereby radially expand the interiorpassageway 18 of the tubular member 13. FIG. 8A illustrates anembodiment in which the sheet 50 has a section wound back and forth intoa plurality of folds 51. A restraining member (not shown) such as anouter sheath or delivery catheter is removed so that the sheet 50unfolds as illustrated in FIG. 8B. The sheet section configured to befolded is preferably a thinner walled or otherwise more flexible thanthe section of the sheet which is not folded. In another embodimentillustrated in FIG. 9A, the sheet 50 is wound around itself into arolled-up configuration having a free edge 52 extending the length ofthe sheet 50, which unrolls to the radially expanded configurationillustrated in FIG. 9B. A variety of suitable unfurling or uncoilingconfigurations may be used in a tubular member which is radiallyexpandable in accordance with the invention including a rolledawning-type mechanism, and the like.

FIG. 16 illustrates a transverse cross sectional view of an alternativeembodiment in which the tubular member 13 comprises a plurality ofinflatable balloons 54 within an outer sheath 55. The balloons 54 can beinflated from a noninflated low profile configuration to an inflatedconfiguration. In the inflated configuration illustrated in FIG. 10,inner passageway 18 is defined between the inflated balloons in part bythe sheath 55. Preferably, three or more balloons 54 are provided to inpart define the inner passageway 18. Balloons 54 are preferably formedof a noncompliant material such as PET, or a complaint material such aspolyethylene having reinforcing members such as wire members. Althoughfour, cylindrical balloons 54 are illustrated in FIG. 10, it should beunderstood that a variety of suitable configurations may be used,including balloons having outer channels such as a spiraled balloondefining an outer spirally extending blood flow channel, similar in manyrespects to perfusion balloons for dilatation. An inflation lumen isprovided in the catheter shaft 11 in fluid communication with balloons54.

FIGS. 10-12 illustrate an alternative embodiment in which tubular member13 comprises a plurality of inflatable fluid-communicating wall chambers56. In the embodiment of FIG. 10, the tubular member 13 comprises aplurality of tubular balloons joined together. For ease of illustration,the radially expandable member 14 which is an inflatable balloon isshown as a transparent material. As best illustrated in FIG. 11 showinga transverse cross sectional view of the tubular member 13 taken alongline 11-11, each tubular balloon 56 is joined to adjacent balloons alonga length thereof, to thereby define the tubular member interiorpassageway 18. As best illustrated in FIG. 12 showing a transverse crosssectional view of the catheter shaft 11 taken along line 12-12, themultilumen shaft 11 defines an inflation lumen 21 in fluid communicationwith balloon 14 on an outer surface of the tubular member 13, an agentdelivery lumen 24 in fluid communication with agent delivery port 25,and a second inflation lumen 57 in fluid communication with the tubularballoons 56. Agent delivery opening 26 adjacent to the shaft agentdelivery port 25 provides a pathway for agent delivery from the lumen 24to exterior to the tubular member 13. The balloons 56 can be bondedtogether using a variety of suitable methods including as adhesive, heatfusion bonding, or solvent bonding such as with hexa-fluoro isopropanol(HFIP) for PET balloons. The tubular member 13 defined by the balloons56 can be deflated and compressed, folded, pleated or otherwise reducedin size for introduction and advancement within the patient's bloodvessel. In a presently preferred embodiment, the pressure required toinflate the balloon 14 is significantly lower than the pressure used toinflate the balloons 56 forming the tubular member 13, so that inflationof the balloon 14 does not deform the tubular member 13.

FIG. 13 illustrates an enlarged distal end of one embodiment having atubular member 13 formed of a plurality of inflatablefluid-communicating wall chambers 56, in which one or more inflationtubes 58 extend from a port in the sidewall of shaft 11 in communicationwith inflation lumen 57 to the distal and/or proximal end of the tubularmember. The inflation tubes 58 are in fluid communication with the wallchambers of the tubular member 13, and are used for delivering inflationfluid into the wall chambers 56 to thereby inflate the tubular member13. In the embodiment of FIG. 13, the inflation tube 58 is secured totubular member 13 by an adapting member or channel 59 at an end of thetubular member 13. One or more agent delivery tubes 60 extend from aport in the shaft 11 in fluid communication with agent delivery lumen 24and into a wall chamber 56 of the tubular member 13. Agent delivery port25 at the distal end of the agent delivery tube 60 extends to and influid communication with an agent delivery opening 26 in a wall defininga wall chamber of the tubular member 13. The section of the agentdelivery tube 60 located within a wall chamber of the tubular member isillustrated in phantom in FIG. 13. Thus, one or more wall chambers ofthe tubular member can be used for agent delivery rather than inflationof the tubular member 13.

In the embodiment illustrated in FIG. 13, the tubular member 13 isconical. The conical tubular member 13 tapers from a large diameterdown-stream end 65 to a smaller diameter up-stream end 66, so that thelarge diameter down-stream end 65 of the tubular member 13 forms theradially expandable member 14. Consequently, a separate radiallyexpandable member 14 is not provided.

The tubular member 13 comprising a plurality of inflatablefluid-communicating wall chambers 56 illustrated in FIG. 13 can beformed by heat sealing or fusing, as for example with a laser, twosheets of a polymeric film together with a plurality of longitudinallyextending seal lines, so that each wall chamber is between adjacent seallines. The seal lines forming the wall chambers do not extend to theproximal most and/or distal most end of the tubular member, so that thewall chambers are in fluid communication with one another. A variety ofsuitable materials can be used to form the sheets including polyolefins,low density polyethylene, polyurethane, polyamides, nylon, polyetherblock amide, polyethylene terephthalate, and other thermoplastics. Thefused sheets are then wrapped into a cylindrical shape and the edgessecured together to form a tubular member 13 which is collapsible andfoldable into a compact configuration for advancement within the bloodvessel. In the embodiments illustrated in FIGS. 10-13, the seal linesdefining the wall chambers of the tubular member 13 extend in straightlines along a length of the tubular member. FIG. 15 illustrates anelevational view of fused sheets 70 for forming an alternativeembodiment of a tubular member 13 in which the wall chambers 56 aredefined by curvilinear seal lines 71 to form interleaved cells, so thata more complete occlusion is provided by the tubular member 13. FIG. 16illustrates a transverse cross-sectional view of an expandedtubular-member 13 formed from the curved seal lines.

FIG. 17 illustrates an alternative embodiment similar to the embodimentshown in FIG. 7 except that the radially expandable member 14 comprisesa radially enlarged section 80 of the tubular member 13. Thus, the frame40, with sheath 41 thereon, forming the tubular member 13 does not havea uniform outer diameter, but instead radially expands from a collapsedconfiguration to define a smaller diameter section 81 defining tubularmember 13, and a larger diameter section 82 defining the radiallyexpandable member 14.

The dimensions of catheter 10 are determined largely by the size of thesize of the blood vessel(s) through which the catheter must pass, andthe size of the blood vessel in which the catheter is deployed. Thelength of the tubular member 13 is typically about 50 to about 150 mm,preferably about 80 to about 120 mm. The tubular member 13 has anunexpanded outer diameter of the tubular member is typically about 1 toabout 5 mm, preferably about 2 to about 4 mm, and a radially expandedouter diameter of about 40 to about 140 mm, preferably about 60 to about120 mm. The radially expanded interior passageway 18 of the tubularmember 13 is typically about 30 to about 130 mm, preferably about 50 toabout 110 mm to provide sufficient perfusion. The interior passageway 18of the tubular member 13 has a radially expanded inner diameter which isabout 1000% to about 6000% larger than the unexpanded inner diameter ofthe passageway 18. The radially expandable member 14 has a length ofabout 10 to about 50 mm, preferably about 20 to about 40 mm. Theexpanded outer diameter of the radially expandable member 14 is about 10to about 35 mm, preferably about 15 to about 30 mm. In the embodimenthaving a conically shaped tubular member 13, the tubular memberdimensions given above should be understood to refer to the distal most(i.e., up-stream) or smaller diameter end of the conical member, unlessotherwise stated. Similarly, in the embodiment in which the radiallyexpandable member 14 comprises the larger diameter end of a conicallyshaped tubular member, the radially expandable member dimensions shouldbe understood to refer to the proximal most (i.e., down-stream) orlarger diameter end of the conical member.

Typically, the shaft 11 has an outer diameter of about 1 to about 5 mm.The inflation lumen 21 has an inner diameter of about 0.02 to about 0.06mm, and the agent delivery lumen has an inner diameter of about 0.01 toabout 0.04 mm. The length of the catheter is about 40 to about 100 cm,preferably about 60 to about 90 cm.

The invention has been discussed in terms of certain preferredembodiments. One of skill in the art will recognize that variousmodifications may be made without departing from the scope of theinvention. Although discussed primarily in terms of controlling bloodflow to a branch vessel such as a renal artery of a blood vessel, itshould be understood that the catheter of the invention could be used todeliver agent to branch vessels other than renal arteries, or to deliverto sites other than branch vessels, as for example where the catheter isused to deliver an agent to the wall defining the body lumen in whichthe catheter is positioned, such as a bile duct, ureter, and the like.Moreover; while certain features may be shown or discussed in relationto a particular embodiment, such individual features may be used on thevarious other embodiments of the invention.

1. A method for enhancing renal function in a patient, comprising:separating a portion of aortic blood flowing into a location within anabdominal aorta into a first blood flow stream that flows along a firstflow path substantially only into a plurality of renal arteries via aplurality of respective ostia having unique respective locations alongthe abdominal aorta wall and a second blood flow stream that flows alonga second flow path across the renal artery ostia and into downstreamcirculation; injecting a volume of fluid agent into the first flow pathwithin the abdominal aorta at the location; wherein the injected fluidagent is delivered substantially only into the plurality of renalarteries via the first flow path into their respective ostia while thesecond blood flow stream flows along the second flow path across therenal artery ostia and into downstream circulation; and wherein thefluid agent being delivered into the plurality of renal arteriescomprises a volume of nifedipine.
 2. The method of claim 1, wherein theinjected fluid agent is delivered substantially only into the pluralityof renal arteries via their respective ostia simultaneously.
 3. Themethod of claim 1, wherein the first flow path passes exterior to atubular member, and the second blood flow path passes within an interiorpassageway of the tubular member.
 4. The method of claim 3, wherein thetubular member tapers from a larger diameter downstream end to a smallerdiameter upstream end.
 5. The method of claim 3, further comprisinginflating the tubular member.
 6. A method for enhancing renal functionin a patient, comprising: separating a portion of aortic blood flowinginto a location within an abdominal aorta into a first blood flow streamthat flows along a first flow path substantially only into a pluralityof renal arteries via a plurality of respective ostia having uniquerespective locations along the abdominal aorta wall and a second bloodflow stream that flows along a second flow path across the renal arteryostia and into downstream circulation; injecting a volume of fluid agentinto the first flow path within the abdominal aorta at the location;wherein the injected fluid agent is delivered substantially only intothe plurality of renal arteries via the first flow path into theirrespective ostia while the second blood flow stream flows along thesecond flow path across the renal artery ostia and into downstreamcirculation; and wherein the fluid agent being delivered into theplurality of renal arteries comprises a volume of Verapamil.
 7. Themethod of claim 6, wherein the injected fluid agent is deliveredsubstantially only into the plurality of renal arteries via theirrespective ostia simultaneously.
 8. The method of claim 6, wherein thefirst flow path passes exterior to a tubular member, and the secondblood flow path passes within an interior passageway of the tubularmember.
 9. The method of claim 8, wherein the tubular member tapers froma larger diameter downstream end to a smaller diameter upstream end. 10.The method of claim 8, further comprising inflating the tubular member.11. A method for enhancing renal function in a patient, comprising:separating a portion of aortic blood flowing into a location within anabdominal aorta into a first blood flow stream that flows along a firstflow path substantially only into a plurality of renal arteries via aplurality of respective ostia having unique respective locations alongthe abdominal aorta wall and a second blood flow stream that flows alonga second flow path across the renal artery ostia and into downstreamcirculation; injecting a volume of fluid agent into the first flow pathwithin the abdominal aorta at the location; wherein the injected fluidagent is delivered substantially only into the plurality of renalarteries via the first flow path into their respective ostia while thesecond blood flow stream flows along the second flow path across therenal artery ostia and into downstream circulation; and wherein thefluid agent being delivered into the plurality of renal arteriescomprises a volume of Fenoldopam.
 12. The method of claim 11, whereinthe injected fluid agent is delivered substantially only into theplurality of renal arteries via their respective ostia simultaneously.13. The method of claim 11, wherein the first flow path passes exteriorto a tubular member, and the second blood flow path passes within aninterior passageway of the tubular member.
 14. The method of claim 13,wherein the tubular member tapers from a larger diameter downstream endto a smaller diameter upstream end.
 15. The method of claim 13 furthercomprising inflating the tubular member.
 16. A method for enhancingrenal function in a patient, comprising: separating a portion of aorticblood flowing into a location within an abdominal aorta into a firstblood flow stream that flows along a first flow path substantially onlyinto a plurality of renal arteries via a plurality of respective ostiahaving unique respective locations along the abdominal aorta wall and asecond blood flow stream that flows along a second flow path across therenal artery ostia and into downstream circulation; injecting a volumeof fluid agent into the first flow path within the abdominal aorta atthe location; wherein the injected fluid agent is deliveredsubstantially only into the plurality of renal arteries via the firstflow path into their respective ostia while the second blood flow streamflows along the second flow path across the renal artery ostia and intodownstream circulation; and wherein the fluid agent being delivered intothe plurality of renal arteries comprises a volume of a dopamine DA₁agonist.
 17. The method of claim 16, wherein the injected fluid agent isdelivered substantially only into the plurality of renal arteries viatheir respective ostia simultaneously.
 18. The method of claim 16,wherein the first flow path passes exterior to a tubular member, and thesecond blood flow path passes within an interior passageway of thetubular member.
 19. The method of claim 18, wherein the tubular membertapers from a larger diameter downstream end to a smaller diameterupstream end.
 20. The method of claim 18, further comprising inflatingthe tubular member.